CCG repeats in cDNAs from human brain
CCG repeats in cDNAs from human brain
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DOI：
10.1007/s004390050889
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发表时间：
1998-12-01
期刊：
影响因子：
5.3
通讯作者：
Margolis, RL
中科院分区：
文献类型：
--
作者：
Kleiderlein, JJ;Nisson, PE;Margolis, RL
三核苷酸重复序列和其他不稳定DNA单位的扩展突变被认为至少是一些神经精神障碍的遗传易感性的原因，包括双相情感障碍、精神分裂症、自闭症和惊恐障碍。为了获得这些和其他疾病的更多候选基因，我们从人脑中高精度地探索了包含CCG、CGC、GCC、CGG、GCG和GGC重复序列(统称为CCG重复序列)的克隆。对18个含有以前未发表的或未描述的重复序列的cDNA进行了染色体定位、重复长度多态以及与已知功能基因的相似性分析。这些cDNA还与GenBank中连续8个或更多CCG三联体的37个人类基因进行了比较。这些重复序列被定位到多个基因座，包括1p34、2p11.2、2q30-32、3p21、3p22、4q35、6q22、7qter、13p13、17q24、18p11、14p13.3、20q12、20q13.3和22q12。在50%的重复序列中检测到长度多态性。新克隆的cDNA没有人类neuresin-1B的完整转录本，BCNG-1(一种新描述的大脑特异离子通道)的一部分，位于鸟核苷酸结合蛋白(G蛋白)β2亚单位5‘UTR军团中的一个以前未报道的多符号重复序列，以及人类版本的鼠富含脯氨酸蛋白7。这一cDNA清单应该会加速寻找与中枢神经系统疾病相关的扩展突变。
Expansion mutations of trinucleotide repeats and other units of unstable DNA have been proposed to account for at least some of the genetic susceptibility to a number of neuropsychiatric disorders, including bipolar affective disorder, schizophrenia, autism, and panic disorder. To generate additional candidate genes for these and other disorders, cDNA libraries from human brain were probed at high stringency for clones containing CCG, CGC, GCC, CGG, GCG, and GGC repeats (referred to collectively as CCG repeats). Some 18 cDNAs containing previously unpublished or uncharacterized repeats were characterized for chromosomal locus, repeat length polymorphism, and similarity to genes of known function. The cDNAs were also compared with the 37 human genes with eight or more consecutive CCG triplets in GenBank. The repeats were mapped to a number of loci, including 1p34, 2p11.2, 2q30-32 3p21, 3p22, 4q35, 6q22, 7qter, 13p13, 17q24, 18p11, 14p13.3, 20q12, 20q13.3, and 22q12. Length polymorphism was detected in 50% of the repeats. The newly cloned cDNAs in elude a complete transcript of human neurexin-1B, a portion of BCNG-1 (a newly described brain-specific ion channel), a previously unreported polymolphic repeat located in the 5' UTR legion of the guanine nucleotide-binding protein (G-protein) beta 2 subunit, and a human version of the mouse proline-rich protein 7. This list of cDNAs should expedite the search for expansion mutations associated with diseases of the central nervous system.